We have isolated bronchial and peripheral airways from guinea pig lungs. 2nd and 3rd generation bronchi respond to histamine, acetylcholine, 5HT, barium and potassium in concentrations similar to those which are effective in tracheal tissues. Bronchi do not relax after anti-inflammatory drug treatment but responses to contractile agonists are markedly potentiated in this tissue. Bronchial tissues develop tensions/dry weight of tissue which are double those seen in tracheal tissues. Cyclic nucleotides in these preparations were determined after chromatography on a cation exchange resin and assayed by radioimmunoassay. Cyclic GMP levels were higher in the bronchus (0.3 plus or minus 0.06 pM/mg protein) than in the trachea (0.15 plus or minus 0.03 pM/mg protein) while cyclic AMP levels were similar (4.7 plus or minus 0.5 pM/mg protein). Histamine (0.1 mu M) increased cyclic GMP by 50% in the bronchus while cyclic AMP was increased 200%. Isoproterenol (10 mu M) similarly increased cyclic AMP levels in the bronchus (12.96 pM/mg protein).